U.S. patent application number 15/691637 was filed with the patent office on 2018-03-01 for method of manufacturing coated beads.
The applicant listed for this patent is Allergan, Inc.. Invention is credited to Alberto FLORES-PUJOL, Matthew B. MILLER, David J. SCHUESSLER, Erik TORJESEN.
Application Number | 20180056261 15/691637 |
Document ID | / |
Family ID | 59982460 |
Filed Date | 2018-03-01 |
United States Patent
Application |
20180056261 |
Kind Code |
A1 |
SCHUESSLER; David J. ; et
al. |
March 1, 2018 |
METHOD OF MANUFACTURING COATED BEADS
Abstract
The present specification discloses methods of making porogen
compositions, methods of making polymer-coated beads, and methods
of making implantable devices that use polymer-coated beads.
Inventors: |
SCHUESSLER; David J.; (Santa
Ana, CA) ; TORJESEN; Erik; (Goleta, CA) ;
FLORES-PUJOL; Alberto; (Heredia, CR) ; MILLER;
Matthew B.; (Hoboken, NJ) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Allergan, Inc. |
Irvine |
CA |
US |
|
|
Family ID: |
59982460 |
Appl. No.: |
15/691637 |
Filed: |
August 30, 2017 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
62381352 |
Aug 30, 2016 |
|
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|
62403465 |
Oct 3, 2016 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61L 31/06 20130101;
B01J 13/125 20130101; A61L 31/10 20130101; A61F 2/12 20130101; A61F
2240/001 20130101; A61L 31/028 20130101; A61F 2/0077 20130101; B01J
2/006 20130101; B01J 2/16 20130101; A61F 2210/0057 20130101; A61F
2002/0081 20130101; A61L 2420/02 20130101 |
International
Class: |
B01J 2/00 20060101
B01J002/00; A61L 31/10 20060101 A61L031/10; A61L 31/02 20060101
A61L031/02; A61L 31/06 20060101 A61L031/06; B01J 2/16 20060101
B01J002/16 |
Claims
1. A process for making polymer-coated beads, the process
comprising: providing a particulate material, the particulate
material comprising particles; depositing the particulate material
into an enclosed zone; fluidizing the particles in the enclosed
zone; introducing an aqueous dispersion into the enclosed zone
containing the fluidized particles, the aqueous dispersion
comprising a polymer component and a solvent component, wherein the
solvent component comprises at least 25% by weight of a nonaqueous
solvent; allowing the aqueous dispersion to coat the fluidized
particles; and allowing or causing the solvent component to
evaporate, thereby leaving a polymer coating on the particles,
wherein the polymer coating is at least about 10 .mu.m thick.
2. The process of claim 1, wherein the particles are spherical.
3. The process of claim 2, wherein the particles are
water-soluble.
4. The process of claim 3, wherein the particles comprise a
salt.
5. The process of claim 4, wherein the salt comprises sodium
chloride.
6. The process of claim 3, wherein the particles comprise a
sugar.
7. The process of claim 6, wherein the sugar comprises sucrose.
8. The process of claim 1, wherein the polymer coating comprises
polyethylene glycol.
9. The process of claim 1, wherein the step of introducing an
aqueous dispersion comprises spraying the aqueous dispersion into
the enclosed zone.
10. The process of claim 9, wherein the aqueous dispersion is
sprayed into the enclosed zone as a bottom spray.
11. The process of claim 9, wherein the aqueous dispersion is
sprayed into the enclosed zone at a rate of between about 25
grams/min and about 65 grams/min.
12. The process of claim 9, wherein the temperature in the enclosed
zone during the spraying is between about 25.degree. C. and about
40.degree. C.
13. The process of claim 1, wherein the nonaqueous solvent
comprises a solvent selected from ethanol, methanol, and
combinations thereof.
14. The process of claim 13, wherein the nonaqueous solvent
comprises ethanol.
15. The process of claim 1, wherein the solvent component comprises
between about 30% and about 80% by weight of a nonaqueous
solvent.
16. The process of claim 1, wherein the solvent component is about
50% by weight ethanol and 50% by weight water.
17. The process of claim 1, wherein the solvent component is about
75% by weight ethanol and 25% by weight water.
18. The process of claim 1, wherein the polymer-coated beads have a
mean circularity of at least about 0.95.
19. The process of claim 1, wherein the polymer-coated beads have a
diameter of about 100 .mu.m to about 1,000 .mu.m.
20. The process of claim 1, wherein the polymer-coated beads have a
diameter of about 500 .mu.m to about 600 .mu.m.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application claims priority to U.S. Provisional
Application No. 62/381,352, filed Aug. 30, 2016, and U.S.
Provisional Application No. 62/403,465, filed Oct. 3, 2016, the
entireties of which are incorporated herein by reference.
BACKGROUND
Field of the Inventions
[0002] The present invention generally relates to methods for
manufacturing coated particles or beads, for example, coated
particles useful for biomedical and other applications.
Description of the Related Art
[0003] The present disclosure relates to processes commonly known
as microencapsulation, fluidized bed coating or Wurster processing.
These technologies are used for precision application of coatings
or films onto particulate materials, such as powders, crystals, or
granules, and other materials. Particulate materials coated with
these processes include for example, solid particles with diameters
ranging from about 30 .mu.m and up to several centimeters, for
example about 100 .mu.m up to about 3 millimeters.
[0004] Generally, in particle coating technologies, particles are
moved around in the fluidized bed and simultaneously sprayed with a
fluid in the form of a solution, suspension or melt. The fluid may
be an aqueous or organic solution, for example, a polymeric
dispersion. Coating can take place as top spray, tangential spray,
or bottom spray or rotor process. Wurster processing generally uses
a bottom spray. As the spray contacts the fluidized particles, the
aqueous or organic solution of the polymer evaporates and the
polymer or other solids it contains forms a thin coating layer or
film on each particle. The processes typically involve evaporative
removal of an aqueous or organic solvent as the film is deposited.
Fluid bed coating processes often include relatively high
fluidizing air volume that is used to both circulate the particles
and evaporate the solvent.
[0005] Wurster processing technology is a common particle coating
technology used in many industries, for example, the pharmaceutical
industry. Wurster particle coating systems described, for example,
in Wurster, U.S. Pat. Nos. 2,648,609, 3,089,824 and 3,253,944,
Jones et al. U.S. Pat. Nos. 5,236,503 and 5,437,889, Jensen U.S.
Pat. No. 6,685,775, and Bender, et al., U.S. Pat. No. 7,147,717.
The entire disclosure of each of these documents is incorporated
herein by reference. Wurster processing is used, for example, for
coating pharmaceutical products such as beads or tablets. This
process is particularly suitable for a controlled release/extended
release and delayed/enteric coating of active ingredients layered
in the form of a pellet or tablet. Advantageously, by using Wurster
processing, a complete sealing of the surface of a particle can be
achieved.
[0006] Particle coating technologies, including Wurster processing,
are useful in other industries as well. For example, films and
coatings are applied as a protective layer to particulate
materials, for example, to increase shelf life or storage stability
of perishable products. Coatings are sometimes applied to particles
as a way to increase or improve functionality of particles, for
example, as a means to mask odors or tastes, or to release specific
active substances.
[0007] Coated particles are described in Liu, et al., U.S. Pat. No.
8,685,296, which is incorporated by reference herein in its
entirety. Liu et al. discusses porogens comprising a core material
and a shell material surrounding the core material, such composite
porogens being useful as a sacrificial material for making textured
breast implant surfaces. Control of the size and/or shape of the
coated particles can be an important factor in this particular
application, in that the textured surfaces of biomedical implants
made with sacrificial particles provides functionality on a
microscopic level. For example, such textured surfaces can be
specifically designed and structured to provide some control over
cell and tissue ingrowth. It should be appreciated that such
biomedical texturing technology could be improved with the
availability of highly uniform, well-structured porogens.
[0008] For some applications of coated particles, the mechanical
properties of the particulate material to be coated are often
relevant and sometimes important considerations. For example, the
surfaces and even the shapes of the particles themselves can affect
quality, consistency and reproducibility of the coating process. In
the case of using porogens as a sacrificial material, it is
important to achieve coated particles with uniform size, shape, and
surfaces, and the coat must have an adequate thickness. In many
applications, highly soluble materials such as salts and sugars are
chosen as particulate materials for the sacrificial particles.
These highly soluble materials are susceptible to chemical and
structural damage by solvents used in the coating process, which
can affect the resultant size, shape, and surface of the coated
particles. Additionally, the susceptibility to damage is increased
when a thicker coating is required due to the prolonged exposure of
the particulate material. Thus, there is a need for developing
methods of coating particles which addresses these problems.
SUMMARY
[0009] In some embodiments of the present disclosure, methods are
provided for controlling or enhancing surface properties of
particulate materials. In some embodiments, methods are provided
for enhancing properties of particulate materials to improve
effectiveness and reproducibility of coating using fluidized bed
technologies, for example, Wurster processing or other coating
processes.
[0010] The presently disclosed processes are able to overcome the
difficulties described above regarding the use of solvents in
coating soluble particulates. The presently disclosed processes
achieve highly spherical polymer-coated beads in which the polymer
coating has a thickness of at least 10 .mu.m, with the polymer
coating showing a smooth surface without significantly damaging the
core particulate material.
[0011] In some embodiments, a process for making polymer-coated
beads is provided comprising providing a particulate material, the
particulate material comprising particles; depositing the
particulate material into an enclosed zone; fluidizing the
particles in the enclosed zone; introducing an aqueous dispersion
into the enclosed zone containing the fluidized particles, the
aqueous dispersion comprising a polymer component and a solvent
component, wherein the solvent component comprises at least 25% by
weight of a nonaqueous solvent; allowing the aqueous dispersion to
coat the fluidized particles; and allowing or causing the solvent
component to evaporate, thereby leaving a polymer coating on the
particles, wherein the polymer coating is at least about 10 .mu.m
thick.
[0012] In some embodiments, a process for manufacturing a soft
prosthetic breast implant is provided, the process comprising:
forming a flexible shell of silicone elastomer, the silicone
elastomer having a thickness; adhering on an exterior of the
flexible shell an even distribution of polymer-coated beads
produced by a process described herein; curing the flexible shell
with the polymer-coated beads adhered thereto; removing the
polymer-coated beads thereby forming an open-pored structure on the
exterior of the flexible shell, such that the exterior of the
flexible shell exhibits an undulating topography, the open-pored
structure comprising round cavities defined by impressions of the
polymer-coated beads; and processing the flexible shell, such that
it forms a closed envelope; wherein the open-pored structure does
not extend through an entire thickness of the silicone
elastomer.
[0013] Additional features and advantages of the subject technology
will be set forth in the description below, and in part will be
apparent from the description, or may be learned by practice of the
subject technology. The advantages of the subject technology will
be realized and attained by the structure particularly pointed out
in the written description and embodiments hereof as well as the
appended drawings.
[0014] It is to be understood that both the foregoing general
description and the following detailed description are exemplary
and explanatory and are intended to provide further explanation of
the subject technology.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] Various features of illustrative embodiments of the
inventions are described below with reference to the drawings. The
illustrated embodiments are intended to illustrate, but not to
limit, the inventions. The drawings contain the following
figures:
[0016] FIG. 1A provides a micrograph of polymer-coated beads
produced according to Experiment 1 in the Example.
[0017] FIG. 1B provides a micrograph of polymer-coated beads
produced according to Experiment 3 in the Example.
[0018] FIG. 1C provides a micrograph of polymer-coated beads
produced according to Experiment 5 in the Example.
[0019] FIG. 1D provides a micrograph of polymer-coated beads
produced according to Experiment 6 in the Example.
[0020] FIG. 1E provides a micrograph of polymer-coated beads
produced according to Experiment 7 in the Example.
[0021] FIG. 1F provides a micrograph of polymer-coated beads
produced according to Experiment 8 in the Example.
[0022] FIG. 1G provides a micrograph of polymer-coated beads
produced according to Experiment 10 in the Example.
[0023] FIG. 1H provides a micrograph of polymer-coated beads
produced according to Experiment 11 in the Example.
[0024] FIG. 2 provides graph showing the average circularity,
average convexity, and the circular equivalent diameter for the
polymer-coated beads produced by experiments of the Example.
DETAILED DESCRIPTION
[0025] It is understood that various configurations of the subject
technology will become readily apparent to those skilled in the art
from the disclosure, wherein various configurations of the subject
technology are shown and described by way of illustration. As will
be realized, the subject technology is capable of other and
different configurations and its several details are capable of
modification in various other respects, all without departing from
the scope of the subject technology. Accordingly, the summary,
drawings and detailed description are to be regarded as
illustrative in nature and not as restrictive.
[0026] The detailed description set forth below is intended as a
description of various configurations of the subject technology and
is not intended to represent the only configurations in which the
subject technology may be practiced. The appended drawings are
incorporated herein and constitute a part of the detailed
description. The detailed description includes specific details for
the purpose of providing a thorough understanding of the subject
technology. However, it will be apparent to those skilled in the
art that the subject technology may be practiced without these
specific details. In some instances, well-known structures and
components are shown in block diagram form in order to avoid
obscuring the concepts of the subject technology Like components
are labeled with identical element numbers for ease of
understanding.
[0027] In some embodiments, a process for making polymer-coated
beads is provided comprising providing a particulate material, the
particulate material comprising particles; depositing the
particulate material into an enclosed zone; fluidizing the
particles in the enclosed zone; introducing an aqueous dispersion
into the enclosed zone containing the fluidized particles, the
aqueous dispersion comprising a polymer component and a solvent
component, wherein the solvent component comprises at least 25% by
weight of a nonaqueous solvent; allowing the aqueous dispersion to
coat the fluidized particles; and allowing or causing the solvent
component to evaporate, thereby leaving a polymer coating on the
particles, wherein the polymer coating is at least about 10 .mu.m
thick.
[0028] In some embodiments, the particulate material is a single
material. In some embodiments, the particulate material can
comprise two or more materials. In some embodiments, the
particulate material comprises an inorganic material. In some
embodiments, the particulate material is water soluble. In some
embodiments, the particulate material comprises an inorganic salt.
In some embodiments, the particulate material comprises a
sugar.
[0029] Useful particulate shapes include, without limitation,
roughly spherical, perfectly spherical, ellipsoidal, polyhedronal,
triangular, pyramidal, quadrilateral like squares, rectangles,
parallelograms, trapezoids, rhombus and kites, and other types of
polygonal shapes. In some embodiments, the particulate material has
a spherical or nearly spherical shape, which enhances the ability
to fluidize the particulate material.
[0030] The particulate material can comprise a natural or
synthetic, inorganic or organic material. Exemplary materials
suitable as a particulate material disclosed herein, include,
without limitation, natural and synthetic salts and its
derivatives, natural and synthetic sugars and its derivatives,
natural and synthetic polysaccharides and its derivatives, natural
and synthetic waxes and its derivatives, natural and synthetic
metals and its derivatives, natural and synthetic organic solids
and its derivatives, natural and synthetic water soluble solids and
its derivatives, and/or natural and synthetic polymers and its
derivatives, composites thereof, and/or combinations thereof.
[0031] The particulate material may be comprised of a single
material disclosed herein or a plurality of materials disclosed
herein. In some embodiments, a particulate material may comprise,
e.g., at least two different materials disclosed herein, at least
three different materials disclosed herein, at least four different
materials disclosed herein, or at least five different materials
disclosed herein. In some embodiments, a particulate material may
comprise, e.g., about 1 to about 2 different materials disclosed
herein, about 1 to about 3 different materials disclosed herein,
about 1 to about 4 different materials disclosed herein, about 1 to
about 5 different materials disclosed herein, about 1 to about 6
different materials disclosed herein, about 2 to about 4 different
materials disclosed herein, about 2 to about 5 different materials
disclosed herein, about 2 to about 6 different materials disclosed
herein, about 3 to about 4 different materials disclosed herein,
about 3 to about 5 different materials disclosed herein, or about 3
to about 6 different materials disclosed herein.
[0032] In some embodiments, the polymer-coated beads comprise a
core particulate material having a particle size of, e.g., about 10
.mu.m, about 20 .mu.m, about 30 .mu.m, about 40 .mu.m, about 50
.mu.m, about 60 .mu.m, about 70 .mu.m, about 80 .mu.m, about 90
.mu.m, about 100 .mu.m, about 200 .mu.m, about 300 .mu.m, about 400
.mu.m, about 500 .mu.m, about 600 .mu.m, about 700 .mu.m, about 800
.mu.m, or about 900 .mu.m. In some embodiments, the polymer-coated
beads comprise a coating having a thickness of, e.g., at least 10
.mu.m, at least 20 .mu.m, at least 30 .mu.m, at least 40 .mu.m, at
least 50 .mu.m, at least 60 .mu.m, at least 70 .mu.m, at least 80
.mu.m, at least 90 .mu.m, at least 100 .mu.m, at least 200 .mu.m,
at least 300 .mu.m, at least 400 .mu.m, at least 500 .mu.m, at
least 600 .mu.m, at least 700 .mu.m, at least 800 .mu.m, or at
least 900 .mu.m. In some embodiments, the polymer-coated beads
comprise a polymer coating having a thickness of, e.g., about 10
.mu.m to about 500 .mu.m, about 10 .mu.m to about 750 .mu.m, about
10 .mu.m to about 1000 .mu.m, about 10 .mu.m to about 2000 .mu.m,
about 10 .mu.m to about 3000 .mu.m, about 25 .mu.m to about 500
.mu.m, about 25 .mu.m to about 750 .mu.m, about 25 .mu.m to about
1000 .mu.m, about 25 .mu.m to about 2000 .mu.m, about 25 .mu.m to
about 3000 .mu.m, about 50 .mu.m to about 500 .mu.m, about 50 .mu.m
to about 750 .mu.m, about 50 .mu.m to about 1000 .mu.m, about 50
.mu.m to about 2000 .mu.m, about 50 .mu.m to about 3000 .mu.m,
about 100 .mu.m to about 500 .mu.m, about 100 .mu.m to about 750
.mu.m, about 100 .mu.m to about 1000 .mu.m, about 100 .mu.m to
about 2000 .mu.m, or about 100 .mu.m to about 3000 .mu.m.
[0033] In some embodiments, the particulate material comprises an
inorganic material. In some embodiments, the particulate material
comprises an organic material. In some embodiments, the particulate
material comprises a salt and/or its derivatives, a sugar and/or
its derivatives, a polysaccharide and/or its derivatives, a wax
and/or its derivatives, a metal and/or its derivatives, a water
soluble solid and/or its derivatives, or a polymer and/or its
derivatives.
[0034] In some embodiments, the particulate material comprises an
inorganic salt particle. The inorganic salt particles can comprise,
for example, any ionic compound that is naturally crystalline, such
as ordinary table salt, i.e., sodium chloride (NaCl). The particles
may comprise, alternatively, potassium chloride or calcium
carbonate, for example, or combinations thereof. Other non-limiting
examples of suitable salts include lithium chloride, magnesium
chloride, calcium chloride, ammonium chloride, sodium iodide,
potassium iodide, lithium iodide, magnesium iodide, calcium iodide,
ammonium iodide, sodium bromide, potassium bromide, lithium
bromide, magnesium bromide, calcium bromide, ammonium bromide,
sodium carbonate, potassium carbonate, lithium carbonate, magnesium
carbonate, ammonium carbonate, sodium bicarbonate, potassium
bicarbonate, lithium bicarbonate, ammonium bicarbonate, sodium
nitrate, potassium nitrate, lithium nitrate, magnesium nitrate,
calcium nitrate, ammonium nitrate, sodium acetate, potassium
acetate, lithium acetate, magnesium acetate, calcium acetate,
ammonium acetate, sodium phosphate, potassium phosphate, lithium
phosphate, magnesium phosphate, calcium phosphate, ammonium
phosphate, sodium sulfate, potassium sulfate, lithium sulfate,
magnesium sulfate, calcium sulfate, or ammonium sulfate, and
combinations thereof. A person of skill in the art will recognize
the suitability several other salt materials not disclosed herein.
For use in the manufacture of medical implants, the salt particles
are preferably biocompatible and safe to use in human beings.
[0035] In some embodiments, the inorganic salt particles are
rounded, spherical, or nearly spherical salt particles. Methods for
producing rounded salt particles have been disclosed in Schuessler
et al., U.S. application Ser. No. 15/607,338, the entirety of which
is incorporated herein by reference.
[0036] A particle's "sphericity" or "mean circularity" can be
determined using the surface area of a sphere having the same
volume as the particle, divided by the actual surface area of the
particle. For example, a sphericity of 1.00 represents a perfect
sphere. Particle sphericities can be determined using a Malvern
(Westborough, Mass., USA) Morphologi G3 ID instrument. Other
methods for measuring the particle's sphericity may be utilized and
will be readily apparent to a person of skill in the art.
[0037] In some embodiments, the salt particles have a sphericity of
greater than 0.750. For example, in some embodiments, the salt
particles have a sphericity of greater than 0.800, greater than
0.850, greater than 0.900, greater than 0.930, or greater than
0.950. In some embodiments, the salt particles have a sphericity of
about 0.950, which provides excellent physical properties that are
superior to angular or cubic shaped particles and useful in a
variety of industries, such as the textile, dairy, food,
fertilizer, paper, pharmaceutical, and medical device
industries.
[0038] The rounded, spherical or nearly spherical salt particles
may have a size, for example, in the range of about 100 .mu.m to
about 1200 .mu.m, about 200 .mu.m to about 1000 .mu.m, about 400
.mu.m to about 800 .mu.m, or about 500 .mu.m to about 700 .mu.m.
The method may provide, for example, such salt particles having a
size or diameter of about 100 .mu.m, about 200 .mu.m, about 300
.mu.m, about 400 .mu.m, about 500 .mu.m, about 600 .mu.m, about 700
.mu.m, about 800 .mu.m, about 900 .mu.m, about 1000 .mu.m, about
1100 .mu.m, or about 1200 .mu.m, depending on the desired use of
the product.
[0039] In some embodiments, the particulate material comprises a
natural or synthetic sugar. In some embodiments, the particulate
material comprises a monomeric sugar compound, i.e., a
monosaccharide. In some embodiments, the particulate material
comprises a polysaccharide of up to 10 monosaccharide units, e.g.,
a disaccharide, a trisaccharide, and an oligosaccharide comprising
four to ten monosaccharide units. Monosaccharides are polyhydroxy
aldehydes or polyhydroxy ketones with three or more carbon atoms,
including aldoses, dialdoses, aldoketoses, ketoses and diketoses,
as well as cyclic forms, deoxy sugars and amino sugars, and their
derivatives, provided that the parent monosaccharide has a
(potential) carbonyl group. Oligosaccharides are compounds in which
at least two monosaccharide units are joined by glycosidic
linkages. According to the number of units, they are called
disaccharides, trisaccharides, tetrasaccharides, pentasaccharides,
hexoaccharides, heptoaccharides, octoaccharides, nonoaccharides,
decoaccharides, etc. An oligosaccharide can be unbranched, branched
or cyclic. Non-limiting examples of sugars include, monosacchrides,
such as, e.g., trioses, like glyceraldehyde and dihydroxyacetone;
tetroses, like erythrose, threose and erythrulose; pentoses, like
arabinose, lyxose, ribose, xylose, ribulose, xylulose; hexoses,
like allose, altrose, galactose, glucose, gulose, idose, mannose,
talose, fructose, psicose, sorbose, tagatose, fucose, rhamnose;
heptoses, like sedoheptulose and mannoheptulose; octooses, like
octulose and 2-keto-3-deoxy-manno-octonate; nonoses like sialose;
and decose; and oligosaccharides, such as, e.g., disaccharides,
like sucrose, lactose, maltose, trehalose, cellobiose, gentiobiose,
kojibiose, laminaribiose, mannobiose, melibiose, nigerose,
rutinose, and xylobiose; trisaccharides like raffinose, acarbose,
maltotriose, and melezitose and/or mixtures thereof. Sugars also
include sugar substitutes like acesulfame potassium, alitame,
aspartame, acesulfame, cyclamate, dulcin, glucin, neohesperidin
dihydrochalcone, neotame, saccharin, and sucralose.
[0040] In some embodiments, the particulate material comprises
rounded, spherical, or nearly spherical sugar particles. In some
embodiments, the spherical sugar particles comprise sucrose. In
some embodiments, the spherical particles comprise starch. In some
embodiments, the spherical particles comprise a combination of
sucrose and starch. Further, in some embodiments, the spherical
particles can comprise about 1% by weight to about 40% by weight,
about 10% by weight to about 30% by weight, or about 15% by weight
to about 25% by weight of starch. In some embodiments, the
spherical particles comprise about 20% by weight of starch.
Spherical sugar particles can be acquired commercially, for
example, the Suglet.RTM. from Colorcon, Inc. (Irvine, Calif.,
USA).
[0041] The particulate material is deposited or placed into an
enclosed zone in preparation for coating the particles. In some
embodiments, the enclosed zone comprises part of an apparatus for
fluid bed coating or Wurster processing. In some embodiments, the
enclosed zone comprises part of an apparatus for microencapsulation
or rotor processing.
[0042] After the particulate material is placed or deposited into
an enclosed zone, the particles are fluidized. As used herein, the
term "fluidization" refers to the process of converting a
particulate material from a static solid-like state to a dynamic
fluid-like state. When fluidized, a bed of solid particles will
behave as a fluid, like a liquid or gas. The fluid properties allow
the particles to conform to the volume of the enclosed zone and to
be transported through enclosed spaces in a similar manner as
liquids and gases.
[0043] The polymer coatings of the present disclosure are applied
to the particulate material through an aqueous dispersion
comprising a polymer component and a solvent component. The solvent
component will comprise at least 25% by weight of a nonaqueous
solvent.
[0044] The polymer component can comprise any suitable polymer for
coating the particulate material. The polymeric component can
comprise natural and synthetic polymers and derivatives thereof.
The polymer component can comprise a single polymeric material or a
plurality of polymeric materials. In some embodiments, the polymer
component can comprise a natural or synthetic elastomer.
[0045] A natural or synthetic elastomer or elastic polymer refers
to an amorphous polymer that exists above its glass transition
temperature at ambient temperatures, thereby conferring the
property of viscoelasticity so that considerable segmental motion
is possible, and includes, without limitation, carbon-based
elastomers, silicon-based elastomers, thermoset elastomers, and
thermoplastic elastomers. As used herein, the term "ambient
temperature" refers to a temperature of about 18.degree. C. to
about 22.degree. C. Elastomers, ether naturally occurring or
synthetically made, comprise monomers usually made of carbon,
hydrogen, oxygen, and/or silicon which are linked together to form
long polymer chains. Elastomers are typically covalently
cross-linked to one another, although non-covalently cross-linked
elastomers are known. Elastomers may be homopolymers or copolymers,
degradable, substantially non-degradable, or non-degradable.
Copolymers may be random copolymers, blocked copolymers, graft
copolymers, and/or mixtures thereof. Unlike other polymers classes,
elastomers can be stretched many times its original length without
breaking by reconfiguring themselves to distribute an applied
stress, and the cross-linkages ensure that the elastomers will
return to their original configuration when the stress is removed.
Elastomers can be a non-medical grade elastomer or a medical grade
elastomer. Medical grade elastomers are typically divided into
three categories: non-implantable, short term implantable and
long-term implantable. Exemplary substantially non-degradable
and/or non-degradable, biocompatible, elastomers include, without
limitation, bromo isobutylene isoprene (BUR), polybutadiene (BR),
chloro isobutylene isoprene (CIIR), polychloroprene (CR),
chlorosulphonated polyethylene (CSM), ethylene propylene (EP),
ethylene propylene diene monomer (EPDM), fluorinated hydrocarbon
(FKM), fluoro silicone (FVQM), hydrogenated nitrile butadiene
(HNBR), polyisoprene (IR), isobutylene isoprene butyl (IIR), methyl
vinyl silicone (MVQ), acrylonitrile butadiene (NBR), polyurethane
(PU), styrene butadiene (SBR), styrene ethylene/butylene styrene
(SEBS), polydimethylsiloxane (PDMS), polysiloxane (SI), and
acrylonitrile butadiene carboxy monomer (XNBR).
[0046] A natural or synthetic polymer and its derivatives, refer to
natural and synthetic macromolecules composed of repeating
structural units typically connected by covalent chemical bonds. A
polymer includes natural or synthetic hydrophilic polymers, natural
or synthetic hydrophobic polymers, natural or synthetic amphiphilic
polymers, degradable polymers, partially degradable polymers,
non-degradable polymers, and combinations thereof. Polymers may be
homopolymers or copolymers. Copolymers may be random copolymers,
blocked copolymers, graft copolymers, and/or mixtures thereof.
Non-limiting examples of polymers include poly(alkylene oxide),
poly(acrylamide), poly(acrylic acid), poly(acrylamide-co-arylic
acid), poly(acrylamide-co-diallyldimethylammonium chloride),
poly(acrylonitrile), poly(allylamine), poly(amide),
poly(anhydride), poly(butylene), poly(.epsilon.-caprolactone),
poly(carbonate), poly(ester), poly(etheretherketone),
poly(ethersulphone), poly(ethylene), poly(ethylene alcohol),
poly(ethylenimine), poly(ethylene glycol), poly(ethylene oxide),
poly(glycolide) ((like poly(glycolic acid)), poly(hydroxy
butyrate), poly(hydroxyethylmethacrylate),
poly(hydroxypropylmethacrylate), poly(hydroxystrene), poly(imide),
poly(lactide), poly(L-lactic acid), poly(D,L-lactic acid),
poly(lactide-co-glycolide), poly(lysine), poly(methacrylate),
poly(methacrylic acid), poly(methylmethacrylate), poly(orthoester),
poly(phenylene oxide), poly(phosphazene), poly(phosphoester),
poly(propylene fumarate), poly(propylene), poly(propylene glycol),
poly(propylene oxide), poly(styrene), poly(sulfone),
poly(tetrafluoroethylene), poly(vinyl acetate), poly(vinyl
alcohol), poly(vinyl chloride), poly(vinylidene fluoride),
poly(vinyl pyrrolidone), poly(urethane), collagen, gelatin, any
copolymer thereof (like poly(ethylene oxide) poly(propylene oxide)
copolymers (poloxamers), poly(vinyl alcohol-co-ethylene),
poly(styrene-co-allyl alcohol, and
poly(ethylene)-block-poly(ethylene glycol), and/or any mixtures
thereof. In some embodiment, the polymer component comprises
polyethylene glycol. In some embodiments, the polymer coating
comprises polyethylene glycol.
[0047] The polymer component and/or polymer coating may be
comprised of a single material disclosed herein or a plurality of
materials disclosed herein. In some embodiments, the polymer
component and/or polymer coating may comprise, e.g., at least two
different materials disclosed herein, at least three different
materials disclosed herein, at least four different materials
disclosed herein, or at least five different materials disclosed
herein. In some embodiments, the polymer component and/or polymer
coating may comprise, e.g., about 1 to about 2 different materials
disclosed herein, about 1 to about 3 different materials disclosed
herein, about 1 to about 4 different materials disclosed herein,
about 1 to about 5 different materials disclosed herein, about 1 to
about 6 different materials disclosed herein, about 2 to about 4
different materials disclosed herein, about 2 to about 5 different
materials disclosed herein, about 2 to about 6 different materials
disclosed herein, about 3 to about 4 different materials disclosed
herein, about 3 to about 5 different materials disclosed herein, or
about 3 to about 6 different materials disclosed herein.
[0048] The polymer coating has a thickness sufficient to allow
formation of a porogen scaffold. As a result, the polymer coating
can be of any thickness, with the proviso that the amount of
polymer is sufficient to create a porogen scaffold useful for its
intended purpose. The thickness of the polymer coating is measured
from the inner surface of the coating that is adjacent of the core
particulate material to the outer surface of the polymer
coating.
[0049] In some embodiments, the polymer-coated beads comprise a
polymer coating having a thickness sufficient to allow formation of
a porogen scaffold. In some embodiments, the polymer-coated beads
comprise a polymer coating having a thickness of, e.g., about 1
.mu.m, about 2 .mu.m, about 3 .mu.m, about 4 .mu.m, about 5 .mu.m,
about 6 .mu.m, about 7 .mu.m, about 8 .mu.m, about 9 .mu.m, about
10 .mu.m, about 15 .mu.m, about 20 .mu.m, about 25 .mu.m, about 30
.mu.m, about 35 .mu.m, about 40 .mu.m, about 45 .mu.m, or about 50
.mu.m. In some embodiments, the polymer-coated beads comprise a
polymer coating having a thickness of, e.g., at least 1 .mu.m, at
least 2 .mu.m, at least 3 .mu.m, at least 4 .mu.m, at least 5
.mu.m, at least 6 .mu.m, at least 7 .mu.m, at least 8 .mu.m, at
least 9 .mu.m, at least 10 .mu.m, at least 15 .mu.m, at least 20
.mu.m, at least 25 .mu.m, at least 30 .mu.m, at least 35 .mu.m, at
least 40 .mu.m, at least 45 .mu.m, or at least 50 .mu.m. In some
embodiments, the polymer-coated beads comprise a polymer coating
having a thickness of, e.g., about 5 .mu.m to about 50 .mu.m, about
5 .mu.m to about 75 .mu.m, about 5 .mu.m to about 100 .mu.m, about
5 .mu.m to about 200 .mu.m, about 5 .mu.m to about 300 .mu.m, about
10 .mu.m to about 50 .mu.m, about 10 .mu.m to about 75 .mu.m, about
10 .mu.m to about 100 .mu.m, about 10 .mu.m to about 200 .mu.m,
about 10 .mu.m to about 300 .mu.m, about 15 .mu.m to about 50
.mu.m, about 15 .mu.m to about 75 .mu.m, about 15 .mu.m to about
100 .mu.m, about 15 .mu.m to about 200 .mu.m, about 15 .mu.m to
about 300 .mu.m, about 25 .mu.m to about 50 .mu.m, about 25 .mu.m
to about 75 .mu.m, about 25 .mu.m to about 100 .mu.m, about 25
.mu.m to about 200 .mu.m, about 25 .mu.m to about 300 .mu.m, about
35 .mu.m to about 50 .mu.m, about 35 .mu.m to about 75 .mu.m, about
35 .mu.m to about 100 .mu.m, about 35 .mu.m to about 200 .mu.m, or
about 35 .mu.m to about 300 .mu.m.
[0050] The solvent component can comprise water and a nonaqueous
solvent. In some embodiments, the nonaqueous solvent is an organic
solvent. In some embodiments, the nonaqueous solvent is miscible
with water. In some embodiments, the nonaqueous solvent is selected
from a C1 to C4 alcohol, acetone, methyl ethylene ketone,
dimethylformamide, ethylene glycol, dichloromethane, chloroform,
and combinations thereof. In some embodiments, the nonaqueous
solvent comprises a solvent selected from ethanol, methanol, and
combinations thereof. In some embodiments, the nonaqueous solvent
comprises ethanol.
[0051] The solvent component comprises at least about 25% by weight
of a nonaqueous solvent. In some embodiments, the solvent component
comprises between about 25% and about 90% by weight of a nonaqueous
solvent. In some embodiments, the solvent component comprises
between about 30% and about 80% by weight of a nonaqueous solvent.
In some embodiments, the solvent component comprises between about
30% and about 80% by weight of a nonaqueous solvent. In some
embodiments, the solvent component comprises between about 40% and
about 70% by weight of a nonaqueous solvent. In some embodiments,
the solvent component comprises between about 40% and about 60% by
weight of a nonaqueous solvent. In some embodiments, the solvent
component comprises between about 45% and about 55% by weight of a
nonaqueous solvent. In some embodiments, the solvent component
comprises between about 50% and about 70% by weight of a nonaqueous
solvent. In some embodiments, the solvent component comprises
between about 50% and about 60% by weight of a nonaqueous solvent.
In some embodiments, the solvent component comprises between about
50% and about 55% by weight of a nonaqueous solvent. In some
embodiments, the solvent component comprises between about 60% and
about 90% by weight of a nonaqueous solvent. In some embodiments,
the solvent component comprises between about 60% and about 80% by
weight of a nonaqueous solvent. In some embodiments, the solvent
component comprises between about 70% and about 80% by weight of a
nonaqueous solvent. In some embodiments, the solvent component is
about 50% by weight ethanol and 50% by weight water. In some
embodiments, the solvent component is about 75% by weight ethanol
and 25% by weight water.
[0052] The polymer component can be present in the aqueous
dispersion in any suitable amount. In some embodiments, the aqueous
dispersion comprises about 1% by weight to about 40% by weight of
the polymer component. In some embodiments, the aqueous dispersion
comprises about 5% by weight to about 35% by weight of the polymer
component. In some embodiments, the aqueous dispersion comprises
about 10% by weight to about 30% by weight of the polymer
component. In some embodiments, the aqueous dispersion comprises
about 15% by weight to about 25% by weight of the polymer
component. In some embodiments, the aqueous dispersion comprises
about 20% by weight to about 30% by weight of the polymer
component. In some embodiments, the aqueous dispersion comprises
about 22% by weight to about 28% by weight of the polymer
component. In some embodiments, the aqueous dispersion comprises
about 24% by weight to about 26% by weight of the polymer
component. In some embodiments, the aqueous dispersion comprises
about 15% by weight, about 16% by weight, about 17% by weight,
about 18% by weight, about 19% by weight, about 20% by weight,
about 21% by weight, about 22% by weight, about 23% by weight,
about 24% by weight, about 25% by weight, about 26% by weight,
about 27% by weight, about 28% by weight, about 29% by weight,
about 30% by weight, about 31% by weight, about 31% by weight,
about 32% by weight, about 33% by weight, about 34% by weight, or
about 35% by weight of the polymer component. In some embodiments,
the aqueous dispersion comprises about 25% by weight of the polymer
component.
[0053] Coating a particle with polymer can be accomplished by any
suitable means, including, without limitation, mechanical
application such as, e.g., dipping, spraying, filtration, knifing,
curtaining, brushing, or vapor deposition; physical adsorption
application; thermal application; fluidization application;
adhering application; chemical bonding application; self-assembling
application; molecular entrapment application, and/or any
combination thereof. The polymer coating is applied to the particle
of core material in such a manner as to coat the particle with the
desired thickness of polymer. Removal of excess polymer material
can be accomplished by any suitable means, including, without
limitation, gravity-based filtering or sieving, vacuum-based
filtering or sieving, blowing, and/or any combination thereof.
[0054] In some embodiments, the aqueous dispersion is introduced
into the enclosed zone in any suitable manner for coating the
particle. In some embodiments, the aqueous dispersion is introduced
into the enclosed zone by spraying, ultrasonic spraying, injecting,
misting, nebulizing, or aerosolizing the aqueous dispersion. In
some embodiments, the step of introducing an aqueous dispersion
comprises spraying the aqueous dispersion into the enclosed zone.
In some embodiments, the aqueous dispersion is sprayed into the
enclosed zone as a top spray, a tangential spray, a bottom spray,
or combinations thereof. In some embodiments, the aqueous
dispersion is sprayed into the enclosed zone as a bottom spray.
[0055] In some embodiments, the aqueous dispersion is sprayed into
the enclosed zone at a rate of between about 25 grams/min and about
65 grams/min. In some embodiments, the aqueous dispersion is
sprayed into the enclosed zone at a rate of between about 25
grams/min and about 45 grams/min. In some embodiments, the aqueous
dispersion is sprayed into the enclosed zone at a rate of between
about 45 grams/min and about 65 grams/min. In some embodiments, the
aqueous dispersion is sprayed into the enclosed zone at a rate of
between about 25 grams/min and about 35 grams/min. In some
embodiments, the aqueous dispersion is sprayed into the enclosed
zone at a rate of between about 35 grams/min and about 45
grams/min. In some embodiments, the aqueous dispersion is sprayed
into the enclosed zone at a rate of between about 55 grams/min and
about 65 grams/min. In some embodiments, the aqueous dispersion is
sprayed into the enclosed zone at a rate of about 25 grams/min,
about 26 grams/min, about 27 grams/min, about 28 grams/min, 29
grams/min, about 30 grams/min, about 31 grams/min, about 32
grams/min, about 33 grams/min, about 34 grams/min, about 35
grams/min, about 36 grams/min, 37 grams/min, about 38 grams/min,
about 39 grams/min, about 40 grams/min, about 41 grams/min, about
42 grams/min, about 43 grams/min, about 44 grams/min, 45 grams/min,
about 46 grams/min, about 47 grams/min, about 48 grams/min, about
49 grams/min, about 50 grams/min, about 51 grams/min, about 52
grams/min, 53 grams/min, about 54 grams/min, about 55 grams/min,
about 56 grams/min, about 57 grams/min, about 58 grams/min, about
59 grams/min, about 60 grams/min, 61 grams/min, about 62 grams/min,
about 63 grams/min, about 64 grams/min, or about 65 grams/min. In
some embodiments, the aqueous dispersion is sprayed into the
enclosed zone at a rate of about 25 grams/min. In some embodiments,
the aqueous dispersion is sprayed into the enclosed zone at a rate
of about 45 grams/min. In some embodiments, the aqueous dispersion
is sprayed into the enclosed zone at a rate of about 65
grams/min.
[0056] In some embodiments, the temperature of the enclosed zone is
controlled while the aqueous dispersion is being introduced or
sprayed therein. In some embodiments, the temperature in the
enclosed zone during the spraying is between about 25.degree. C.
and about 40.degree. C. In some embodiments, the temperature in the
enclosed zone during the spraying is between about 25.degree. C.
and about 35.degree. C. In some embodiments, the temperature in the
enclosed zone during the spraying is between about 25.degree. C.
and about 30.degree. C. In some embodiments, the temperature in the
enclosed zone during the spraying is between about 30.degree. C.
and about 40.degree. C. In some embodiments, the temperature in the
enclosed zone during the spraying is between about 35.degree. C.
and about 40.degree. C. In some embodiments, the temperature in the
enclosed zone during the spraying is about 25.degree. C., about
26.degree. C., about 27.degree. C., about 28.degree. C., about
29.degree. C., about 30.degree. C., about 31.degree. C., about
32.degree. C., about 33.degree. C., about 34.degree. C., about
35.degree. C., about 36.degree. C., about 37.degree. C., about
38.degree. C., about 39.degree. C., or about 40.degree. C.
[0057] After the aqueous dispersion is introduced into the enclosed
zone, it will contact the fluidized particles contained therein.
The polymer coating forms as the solvent component of the aqueous
dispersion become devolitized. As used herein, the term
"devolitalizing" or "devolitalization" refers to a process that
removes volatile components (e.g., solvent component) from a
substance base (e.g., aqueous dispersion) or a particle coated with
the aqueous dispersion and/or the forming polymer layer.
Devolitalization of a substance base and/or a particle coated with
the aqueous dispersion and/or the forming polymer layer can be
accomplished by any suitable means that substantially all the
volatile components are removed from the resultant polymer-coated
beads. Non-limiting examples of devolitalizing procedures include
evaporation, freeze-drying, sublimation, extraction, and/or any
combination thereof. The application of these techniques will be
readily apparent to a person of ordinary skill in the art. In some
embodiments, the aqueous dispersion is devolitized by allowing the
solvent component to evaporate. In some embodiments, the aqueous
dispersion is devolitized by evaporating the solvent component at
an increased temperature such as the temperatures listed above that
are maintained while spraying the aqueous dispersion.
[0058] In some embodiments, the process for making polymer-coated
beads will have a duration of about 1 hour to about 10 hours. In
some embodiments, the process for making polymer-coated beads will
have a duration of about 2 hour to about 9 hours. In some
embodiments, the process for making polymer-coated beads will have
a duration of about 3 hour to about 8 hours. In some embodiments,
the process for making polymer-coated beads will have a duration of
about 4 hour to about 7 hours. In some embodiments, the process for
making polymer-coated beads will have a duration of about 5 hour to
about 8 hours. In some embodiments, the process for making
polymer-coated beads will have a duration of about 6 hour to about
8 hours. In some embodiments, the process for making polymer-coated
beads will have a duration of at least about 1 hour. In some
embodiments, the process for making polymer-coated beads will have
a duration of at least about 2 hours. In some embodiments, the
process for making polymer-coated beads will have a duration of at
least about 3 hours. In some embodiments, the process for making
polymer-coated beads will have a duration of at least about 4
hours. In some embodiments, the process for making polymer-coated
beads will have a duration of at least about 5 hours. In some
embodiments, the process for making polymer-coated beads will have
a duration of at least about 6 hours. In some embodiments, the
process for making polymer-coated beads will have a duration of at
least about 7 hours. In some embodiments, the process for making
polymer-coated beads will have a duration of at least about 8
hours. In some embodiments, the process for making polymer-coated
beads will have a duration of at least about 9 hours.
[0059] In some embodiments, the polymer-coated beads have a
sphericity of greater than 0.750. For example, in some embodiments,
the polymer-coated beads have a sphericity of greater than 0.800,
greater than 0.850, greater than 0.900, greater than 0.930, or
greater than 0.950. In some embodiments, the polymer-coated beads
have a sphericity of about 0.950, which provides excellent physical
properties that are superior to angular or cubic shaped particles
and useful in a variety of industries, such as the textile, dairy,
food, fertilizer, paper, pharmaceutical, and medical device
industries.
[0060] In some embodiments, rounded, spherical or nearly spherical
polymer-coated beads may have a size, for example, in the range of
about 100 .mu.m to about 1200 .mu.m, about 200 .mu.m to about 1000
.mu.m, about 400 .mu.m to about 800 .mu.m, or about 500 .mu.m to
about 700 .mu.m. The method may provide, for example, such
polymer-coated beads having a size or diameter of about 100 .mu.m,
about 200 .mu.m, about 300 .mu.m, about 400 .mu.m, about 500 .mu.m,
about 600 .mu.m, about 700 .mu.m, about 800 .mu.m, about 900 .mu.m,
about 1000 .mu.m, about 1100 .mu.m, or about 1200 .mu.m, depending
on the desired use of the product.
Medical Implants
[0061] In some embodiments, the methods disclosed herein can
provide polymer-coated beads useful for texturing medical implants,
for example, breast implants. The polymer-coated beads can have a
size of about 400 .mu.m to about 600 .mu.m, for example, about 500
.mu.m. Methods for applying porogens or sacrificial particles such
as polymer-coated beads in the manufacture of textured medical
implants are described in detail in U.S. Pat. No. 8,313,527, the
entirety of which is incorporated herein by reference. A person of
skill in the art would understand how to apply the polymer-coated
beads formed from the processes described herein as a sacrificial
material in the processes for manufacturing these and other medical
implants in which a surface texture or other attribute may be
desirable.
[0062] For example, in some embodiments, a breast implant having an
elastomeric silicone shell can be processed to create a desired
surface texture by using polymer-coated beads as a sacrificial
material. The polymer-coated beads can be those produced by the
present methods.
[0063] The processes for forming the breast implant generally
comprise the steps of forming a flexible shell, adhering on the
exterior of the flexible shell a distribution of polymer-coated
beads, curing the flexible shell with the polymer-coated beads
adhered thereto, and causing or allowing the polymer-coated beads
to be removed from the shell thereby leaving impressions of the
particles in the shell to create an open-pored structure on a
surface thereof.
[0064] In some embodiments, the flexible shell is formed of a
silicone elastomer. For instance, the flexible shell may be formed
of a plurality of layers of different silicone elastomers, or the
flexible shell may be formed of a single homogeneous layer of a
silicone elastomer.
[0065] In some embodiments, the step of forming the flexible shell
may comprise dipping a mandrel into a liquid dispersion of
elastomeric material. Alternatively, the step of forming comprises
rotational molding.
[0066] In some embodiments, the step of adhering comprises dipping
the flexible shell into a liquid containing the polymer-coated
beads, for example, a liquid dispersion or emulsion of
polymer-coated beads. Prior to the step of dipping the flexible
shell, the process may also include applying a tack coat layer onto
the flexible shell.
[0067] In some embodiments, the solvent is an aqueous composition,
for example, water. In some embodiments, the polymer-coated beads
comprise a suitable solid material, which is provided in a rounded
particulate form, and which is capable of being adhered to a shell,
for example, an uncured elastomer shell, and is capable of being
dissolved, for example, using a solvent, thereby leaving open,
rounded pores in the shell.
[0068] In some embodiments, the polymer-coated beads have a
substantially uniform particle size of between about 150 .mu.m and
about 1450 .mu.m. More specifically, the beads have a maximum
particle size range selected from a group of ranges consisting of
(1) a range between about 180 .mu.m and about 425 .mu.m, (2) a
range between about 425 .mu.m and about 850 .mu.m, and (3) a range
between about 850 .mu.m and about 1450 .mu.m. In some embodiments,
about 90% of the particles are in the selected particle size range.
Size selection can be accomplished by sieving with the desired size
sieve(s).
[0069] In some embodiments, a soft prosthetic breast implant can be
formed by a process comprising the steps of forming a flexible
shell of silicone elastomer in the shape of a breast implant,
adhering on the exterior of the flexible shell a substantially even
distribution of polymer-coated beads, curing the flexible shell
with the polymer-coated beads adhered thereto, and exposing the
flexible shell to a suitable solvent for a sufficient amount of
time to dissolve the polymer-coated beads thereby forming an
open-pored structure on the exterior of the flexible shell.
[0070] In accordance with some embodiments, an implant formed in
accordance with the present process can be far superior to an
implant made using conventional porogens or sacrificial materials.
For example, in some embodiments, at least one, at least two, or
all three of the physical properties of ultimate break force,
ultimate elongation, or ultimate tensile strength of an implant
formed in accordance with the present process can be superior to an
implant made using substantially the same process and the same
materials but using a different porogen/sacrificial material than
the presently disclosed polymer-coated beads.
[0071] The step of forming the flexible shell may comprise dipping
a mandrel into a liquid dispersion of a shell material, or
rotational molding. In some embodiments, the step of forming the
flexible shell comprises forming a shell with an opening and the
process further includes attaching a patch to cover the opening.
The patch may be an unvulcanized elastomer and is attached prior to
the step of curing. Alternatively, the step of forming the flexible
shell comprises forming a shell with an opening and the process
further includes attaching a valve, for example, a one-way valve to
cover the opening. The polymer-coated beads may comprise a sugar,
for example sucrose, and polyethylene glycol.
Example
[0072] The following Example is provided for illustrative purposes
only, and is not intended to be limiting of the scope of the
present disclosure.
[0073] Eleven designs of experiment ("DOE") were conducted for
coating rounded sugar particles with the parameters as listed in
Table 1.
TABLE-US-00001 TABLE 1 Experimental Parameters for polymer-coating
process Experiment Temper- Spray Nonaqueous Solvent (DOE) No. ature
(.degree. C.) Rate (g/min) Content (wt %) 1 25.0 65 50 2 32.5 45 75
3 40.0 25 100 4 32.5 45 75 5 25.0 25 100 6 40.0 25 50 7 25.0 65 100
8 40.0 65 100 9 32.5 45 75 10 25.0 25 50 11 40.0 65 50
[0074] For each experiment, 15 kg of sugar spheres, U.S. mesh size
35-40, were Wurster-coated in a Fluid Bed System Model GPCG-15
(Glatt Air Techniques, Germany), with 2 kg of polyethylene glycol
("PEG") dissolved in 6 kg of solvent mixture. The solvent
(ethanol:water) mixtures were 50:50, 75:25, or 100:0. The spray
rates were 25 g/min, 45 g/min, or 65 g/min, and the temperature was
set at 25.degree. C., 32.5.degree. C., or 40.degree. C. Coated
particles were screened with 18-mesh and 60-mesh to remove
oversized and undersized (i.e., fines) materials. To compare the
surface morphologies, the PEG-coated sugar spheres from each
experiment were analyzed under light microscope.
[0075] The coated particles were also analyzed using a Malvern
Morphologi.RTM. G3 to determine the particles' circular equivalent
diameter, convexity, and circularity. The percentage of fines
recovered was also assessed.
[0076] FIGS. 1A-1H provide micrographs of the particles produced by
Experiments 1 (FIG. 1A), 3 (FIG. 1B), 5 (FIG. 1C), 6 (FIG. 1D), 7
(1E), 8 (FIG. 1F), 10 (FIG. 1G), and 11 (FIG. 1H). An analysis of
these micrographs indicated that the surface morphology of
Experiments 3, 5, 7, and 8, which were coated using 100% ethanol
solvent, appeared more crystalline compared to the other
experiments. In addition, Experiments 5, 7, and 8 had the highest
percentages of fines. The micrograph for Experiment 1 (FIG. 1A)
showed beads having a bumpy coating. Micrographs of Experiments 10
(FIG. 1G) and 11 (FIG. 1H) showed particles with the smoothest
surfaces and higher average convexities and circularities compared
to the other 9 batches of coated sugar spheres.
[0077] A graph of the circularity and convexity analyses of the
polymer-coated beads from Experiments 1-11 is provided in FIG. 2.
This graphs shows that Experiments 7, 8, and 5 yielded the least
circular beads and lowest average convexity among the 11
experiments. Although Experiment 6 had the highest average
circularity, it generated some fines and had a smaller mean
diameter. The results of the experiments indicates that coating
that yielded the best surface properties was achieved when the
coating solutions were prepared with at least 50% ethanol, for
example, 50% ethanol.
Illustration of Subject Technology as Clauses
[0078] Various examples of aspects of the disclosure are described
as numbered clauses (1, 2, 3, etc.) for convenience. These are
provided as examples, and do not limit the subject technology.
Identifications of the figures and reference numbers are provided
below merely as examples and for illustrative purposes, and the
clauses are not limited by those identifications.
[0079] Clause 1. A process for making polymer-coated beads, the
process comprising: providing a particulate material, the
particulate material comprising particles; depositing the
particulate material into an enclosed zone; fluidizing the
particles in the enclosed zone; introducing an aqueous dispersion
into the enclosed zone containing the fluidized particles, the
aqueous dispersion comprising a polymer component and a solvent
component, wherein the solvent component comprises at least 25% by
weight of a nonaqueous solvent; allowing the aqueous dispersion to
coat the fluidized particles; and allowing or causing the solvent
component to evaporate, thereby leaving a polymer coating on the
particles, wherein the polymer coating is at least about 10 .mu.m
thick.
[0080] Clause 2. The process of Clause 1, wherein the particles are
spherical.
[0081] Clause 3. The process of Clause 1 or Clause 2, wherein the
particles are water-soluble.
[0082] Clause 4. The process of Clause 3, wherein the particles
comprise a salt.
[0083] Clause 5. The process of Clause 4, wherein the salt is
selected from the group consisting of sodium chloride, potassium
chloride, lithium chloride, magnesium chloride, calcium chloride,
ammonium chloride, sodium iodide, potassium iodide, lithium iodide,
magnesium iodide, calcium iodide, ammonium iodide, sodium bromide,
potassium bromide, lithium bromide, magnesium bromide, calcium
bromide, ammonium bromide, sodium carbonate, potassium carbonate,
lithium carbonate, magnesium carbonate, ammonium carbonate, sodium
bicarbonate, potassium bicarbonate, lithium bicarbonate, ammonium
bicarbonate, sodium nitrate, potassium nitrate, lithium nitrate,
magnesium nitrate, calcium nitrate, ammonium nitrate, sodium
acetate, potassium acetate, lithium acetate, magnesium acetate,
calcium acetate, ammonium acetate, sodium phosphate, potassium
phosphate, lithium phosphate, magnesium phosphate, calcium
phosphate, ammonium phosphate, sodium sulfate, potassium sulfate,
lithium sulfate, magnesium sulfate, calcium sulfate, ammonium
sulfate, and combinations thereof.
[0084] Clause 6. The process of Clause 5, wherein the salt
comprises sodium chloride.
[0085] Clause 7. The process of Clause 3, wherein the particles
comprise a sugar.
[0086] Clause 8. The process of Clause 7, wherein the sugar is
selected from the group consisting of sucrose, fructose, lactose,
galactose, mannose, dextrose, glucose, and combinations
thereof.
[0087] Clause 9. The process of Clause 8, wherein the sugar
comprises sucrose.
[0088] Clause 10. The process of any one of the preceding Clauses,
wherein the polymer coating comprises a polymer selected from the
group consisting of poly(alkylene oxide), poly(acrylamide),
poly(acrylic acid), poly(acrylamide-co-acrylic acid),
poly(acrylamide-co-diallyldimethylammonium chloride),
poly(acrylonitrile), poly(allylamine), poly(amide),
poly(anhydride), poly(butylene), poly(.epsilon.-caprolactone),
poly(carbonate), poly(ester), poly(etheretherketone),
poly(ethersulphone), poly(ethylene), poly(ethylene alcohol),
poly(ethylenimine), polyethylene glycol, poly(ethylene oxide),
poly(glycolide) ((like poly(glycolic acid)), poly(hydroxy
butyrate), poly(hydroxyethylmethacrylate),
poly(hydroxypropylmethacrylate), poly(hydroxystyrene), poly(imide),
poly(lactide), poly(L-lactic acid), poly(D,L-lactic acid),
poly(lactide-co-glycolide), poly(lysine), poly(methacrylate),
poly(methacrylic acid), poly(methylmethacrylate), poly(orthoester),
poly(phenylene oxide), poly(phosphazene), poly(phosphoester),
poly(propylene fumarate), poly(propylene), poly(propylene glycol),
poly(propylene oxide), poly(styrene), poly(sulfone),
poly(tetrafluoroethylene), poly(vinyl acetate), poly(vinyl
alcohol), poly(vinyl chloride), poly(vinylidene fluoride),
poly(vinyl pyrrolidone), poly(urethane), collagen, gelatin, any
copolymer thereof (like poly(ethylene oxide) poly(propylene oxide)
copolymers (poloxamers), poly(vinyl alcohol-co-ethylene),
poly(styrene-co-allyl alcohol, and
poly(ethylene)-block-poly(ethylene glycol), and/or any mixtures
thereof.
[0089] Clause 11. The process of Clause 10, wherein the polymer
coating comprises polyethylene glycol.
[0090] Clause 12. The process of any one of the preceding Clauses,
wherein the step of introducing an aqueous dispersion into the
enclosed zone comprises spraying, injecting, misting, nebulizing,
or aerosolizing the aqueous dispersion.
[0091] Clause 13. The process of Clause 12, wherein the step of
introducing an aqueous dispersion comprises spraying the aqueous
dispersion into the enclosed zone.
[0092] Clause 14. The process of Clause 13, wherein the aqueous
dispersion is sprayed into the enclosed zone as a top spray, a
tangential spray, a bottom spray, or combinations thereof.
[0093] Clause 15. The process of Clause 14, wherein the aqueous
dispersion is sprayed into the enclosed zone as a bottom spray.
[0094] Clause 16. The process of any one of Clauses 13 to 15,
wherein the aqueous dispersion is sprayed into the enclosed zone at
a rate of between about 25 grams/min and about 65 grams/min.
[0095] Clause 17. The process of any one of Clauses 13 to 16,
wherein the temperature in the enclosed zone during the spraying is
between about 25.degree. C. and about 40.degree. C.
[0096] Clause 18. The process of any one of the preceding Clauses,
wherein the nonaqueous solvent comprises a solvent selected from a
C1 to C4 alcohol, acetone, methyl ethylene ketone,
dimethylformamide, ethylene glycol, dichloromethane, chloroform,
and combinations thereof.
[0097] Clause 19. The process of Clause 17, wherein the nonaqueous
solvent comprises a solvent selected from ethanol, methanol, and
combinations thereof.
[0098] Clause 20. The process of Clause 19, wherein the nonaqueous
solvent comprises ethanol.
[0099] Clause 21. The process of any one of the preceding Clauses,
wherein the solvent component comprises between about 25% and about
90% by weight of a nonaqueous solvent.
[0100] Clause 22. The process of Clause 21, wherein the solvent
component comprises between about 30% and about 80% by weight of a
nonaqueous solvent.
[0101] Clause 23. The process of Clause 21, wherein the solvent
component comprises between about 40% and about 60% by weight of a
nonaqueous solvent.
[0102] Clause 24. The process of Clause 21, wherein the solvent
component comprises between about 50% and about 60% by weight of a
nonaqueous solvent.
[0103] Clause 25. The process of Clause 21, wherein the solvent
component comprises between about 45% and about 55% by weight of a
nonaqueous solvent.
[0104] Clause 26. The process of Clause 21, wherein the solvent
component comprises between about 60% and about 90% by weight of a
nonaqueous solvent.
[0105] Clause 27. The process of Clause 21, wherein the solvent
component comprises between about 60% and about 80% by weight of a
nonaqueous solvent.
[0106] Clause 28. The process of Clause 21, wherein the solvent
component comprises between about 70% and about 80% by weight of a
nonaqueous solvent.
[0107] Clause 29. The process of Clause 21, wherein the solvent
component is about 50% by weight ethanol and 50% by weight
water.
[0108] Clause 30. The process of Clause 21, wherein the solvent
component is about 75% by weight ethanol and 25% by weight
water.
[0109] Clause 31. The process of any one of the preceding Clauses,
wherein the polymer-coated beads have a mean circularity of at
least about 0.6.
[0110] Clause 32. The process of any one of the preceding Clauses,
wherein the polymer-coated beads have a mean circularity of at
least about 0.7.
[0111] Clause 33. The process of any one of the preceding Clauses,
wherein the polymer-coated beads have a mean circularity of at
least about 0.80.
[0112] Clause 34. The process of any one of the preceding Clauses,
wherein the polymer-coated beads have a mean circularity of at
least about 0.90.
[0113] Clause 35. The process of any one of the preceding Clauses,
wherein the polymer-coated beads have a mean circularity of at
least about 0.95.
[0114] Clause 36. The process of any one of the preceding Clauses,
wherein the polymer-coated beads have a diameter of about 100 .mu.m
to about 1,000 .mu.m.
[0115] Clause 37. The process of any one of the preceding Clauses,
wherein the polymer-coated beads have a diameter of about 200 .mu.m
to about 900 .mu.m.
[0116] Clause 38. The process of any one of the preceding Clauses,
wherein the polymer-coated beads have a diameter of about 300 .mu.m
to about 800 .mu.m.
[0117] Clause 39. The process of any one of the preceding Clauses,
wherein the polymer-coated beads have a diameter of about 400 .mu.m
to about 700 .mu.m.
[0118] Clause 40. The process of any one of the preceding Clauses,
wherein the polymer-coated beads have a diameter of about 500 .mu.m
to about 600 .mu.m.
[0119] Clause 41. The process of any one of the preceding Clauses,
wherein the polymer coating is at least about 15 .mu.m thick.
[0120] Clause 42. The process of any one of the preceding Clauses,
wherein the polymer coating is at least about 20 .mu.m thick.
[0121] Clause 43. The process of any one of the preceding Clauses,
wherein the polymer coating is at least about 25 .mu.m thick.
[0122] Clause 44. The process of any one of the preceding Clauses,
wherein the polymer coating is at least about 30 .mu.m thick.
[0123] Clause 45. The process of any one of the preceding Clauses,
wherein the aqueous dispersion comprises about 1% by weight to
about 40% by weight of the polymer component.
[0124] Clause 46. The process of any one of the preceding Clauses,
wherein the aqueous dispersion comprises about 20% by weight to
about 30% by weight of the polymer component.
[0125] Clause 47. The process of any one of the preceding Clauses,
wherein the aqueous dispersion comprises about 25% by weight of the
polymer component.
[0126] Clause 48. The process of any one of the preceding Clauses,
wherein the process has a duration of about 1 hour to about 10
hours.
[0127] Clause 49. The process of any one of the preceding Clauses,
wherein the process has a duration of at least about 4 hours.
[0128] Clause 50. The process of any one of the preceding Clauses,
wherein the process has a duration of at least about 6 hours.
[0129] Clause 51. The process of any one of the preceding Clauses,
wherein the enclosed zone comprises part of an apparatus for
fluidized bed coating.
[0130] Clause 52. A polymer-coated bead produced by the process of
any one of the preceding Clauses.
[0131] Clause 53. A process for manufacturing a soft prosthetic
breast implant, the process comprising: forming a flexible shell of
silicone elastomer, the silicone elastomer having a thickness;
adhering on an exterior of the flexible shell an even distribution
of the polymer-coated beads of Clause 52; curing the flexible shell
with the polymer-coated beads adhered thereto; removing the
polymer-coated beads thereby forming an open-pored structure on the
exterior of the flexible shell, such that the exterior of the
flexible shell exhibits an undulating topography, the open-pored
structure comprising round cavities defined by impressions of the
polymer-coated beads; and processing the flexible shell, such that
it forms a closed envelope; wherein the open-pored structure does
not extend through an entire thickness of the silicone
elastomer.
FURTHER CONSIDERATIONS
[0132] In some embodiments, any of the clauses herein may depend
from any one of the independent clauses or any one of the dependent
clauses. In one aspect, any of the clauses (e.g., dependent or
independent clauses) may be combined with any other one or more
clauses (e.g., dependent or independent clauses). In one aspect, a
claim may include some or all of the words (e.g., steps,
operations, means or components) recited in a clause, a sentence, a
phrase or a paragraph. In one aspect, a claim may include some or
all of the words recited in one or more clauses, sentences, phrases
or paragraphs. In one aspect, some of the words in each of the
clauses, sentences, phrases or paragraphs may be removed. In one
aspect, additional words or elements may be added to a clause, a
sentence, a phrase or a paragraph. In one aspect, the subject
technology may be implemented without utilizing some of the
components, elements, functions or operations described herein. In
one aspect, the subject technology may be implemented utilizing
additional components, elements, functions or operations.
[0133] The foregoing description is provided to enable a person
skilled in the art to practice the various configurations described
herein. While the subject technology has been particularly
described with reference to the various figures and configurations,
it should be understood that these are for illustration purposes
only and should not be taken as limiting the scope of the subject
technology.
[0134] There may be many other ways to implement the subject
technology. Various functions and elements described herein may be
partitioned differently from those shown without departing from the
scope of the subject technology. Various modifications to these
configurations will be readily apparent to those skilled in the
art, and generic principles defined herein may be applied to other
configurations. Thus, many changes and modifications may be made to
the subject technology, by one having ordinary skill in the art,
without departing from the scope of the subject technology.
[0135] It is understood that the specific order or hierarchy of
steps in the processes disclosed is an illustration of exemplary
approaches. Based upon design preferences, it is understood that
the specific order or hierarchy of steps in the processes may be
rearranged. Some of the steps may be performed simultaneously. The
accompanying method claims present elements of the various steps in
a sample order, and are not meant to be limited to the specific
order or hierarchy presented.
[0136] As used herein, the phrase "at least one of" preceding a
series of items, with the term "and" or "or" to separate any of the
items, modifies the list as a whole, rather than each member of the
list (i.e., each item). The phrase "at least one of" does not
require selection of at least one of each item listed; rather, the
phrase allows a meaning that includes at least one of any one of
the items, and/or at least one of any combination of the items,
and/or at least one of each of the items. By way of example, the
phrases "at least one of A, B, and C" or "at least one of A, B, or
C" each refer to only A, only B, or only C; any combination of A,
B, and C; and/or at least one of each of A, B, and C.
[0137] Terms such as "top," "bottom," "front," "rear" and the like
as used in this disclosure should be understood as referring to an
arbitrary frame of reference, rather than to the ordinary
gravitational frame of reference. Thus, a top surface, a bottom
surface, a front surface, and a rear surface may extend upwardly,
downwardly, diagonally, or horizontally in a gravitational frame of
reference.
[0138] Furthermore, to the extent that the term "include," "have,"
or the like is used in the description or the claims, such term is
intended to be inclusive in a manner similar to the term "comprise"
as "comprise" is interpreted when employed as a transitional word
in a claim.
[0139] In one or more aspects, the terms "about," "substantially,"
and "approximately" may provide an industry-accepted tolerance for
their corresponding terms and/or relativity between items, such as
from less than one percent to five percent.
[0140] The word "exemplary" is used herein to mean "serving as an
example, instance, or illustration." Any embodiment described
herein as "exemplary" is not necessarily to be construed as
preferred or advantageous over other embodiments.
[0141] A reference to an element in the singular is not intended to
mean "one and only one" unless specifically stated, but rather "one
or more." Pronouns in the masculine (e.g., his) include the
feminine and neuter gender (e.g., her and its) and vice versa. The
term "some" refers to one or more. Underlined and/or italicized
headings and subheadings are used for convenience only, do not
limit the subject technology, and are not referred to in connection
with the interpretation of the description of the subject
technology. All structural and functional equivalents to the
elements of the various configurations described throughout this
disclosure that are known or later come to be known to those of
ordinary skill in the art are expressly incorporated herein by
reference and intended to be encompassed by the subject technology.
Moreover, nothing disclosed herein is intended to be dedicated to
the public regardless of whether such disclosure is explicitly
recited in the above description.
[0142] Although the detailed description contains many specifics,
these should not be construed as limiting the scope of the subject
technology but merely as illustrating different examples and
aspects of the subject technology. It should be appreciated that
the scope of the subject technology includes other embodiments not
discussed in detail above. Various other modifications, changes and
variations may be made in the arrangement, operation and details of
the method and apparatus of the subject technology disclosed herein
without departing from the scope of the present disclosure. Unless
otherwise expressed, reference to an element in the singular is not
intended to mean "one and only one" unless explicitly stated, but
rather is meant to mean "one or more." In addition, it is not
necessary for a device or method to address every problem that is
solvable (or possess every advantage that is achievable) by
different embodiments of the disclosure in order to be encompassed
within the scope of the disclosure. The use herein of "can" and
derivatives thereof shall be understood in the sense of "possibly"
or "optionally" as opposed to an affirmative capability.
* * * * *